title: The effects of DISC1 risk variants on brain activation in controls, patients with bipolar disorder and patients with schizophrenia.
abstract: Three risk variants (rs1538979, rs821577, and rs821633) in the Disrupted-in-Schizophrenia-1 (DISC1) gene have previously been associated with both schizophrenia and bipolar disorder in a recent collaborative analysis of European cohorts. In this study we examined the effects of these risk variants on brain activation during functional magnetic resonance imaging (fMRI) of the Hayling Sentence Completion Task (HSCT) in healthy volunteers (n=33), patients with schizophrenia (n=20) and patients with bipolar disorder (n=36). In the healthy controls the risk associated allele carriers of SNPs rs1538979 and rs821633 demonstrated decreased activation of the cuneus. Moreover, there was an effect of SNP rs1538979 in the pre/postcentral gyrus with decreased activation in healthy controls and increased activation in patients with schizophrenia. In the bipolar group there was decreased activation in the risk carriers of SNP rs821633 in the inferior parietal lobule and left cingulate cortex. Clusters in the precentral gyrus, left middle temporal gyrus and left cerebellum were found to be significant on examining the group × genotype interactions. These findings may provide a better understanding of the neural effects of DISC1 variants and on the pathophysiology of schizophrenia and bipolar disorder.
authors.affiliation: The University of Edinburgh, Royal Edinburgh Hospital, Edinburgh, Scotland, UK. G.Chakirova@sms.ed.ac.uk
authors.forename: Goultchira
authors.initials: G
authors.lastname: Chakirova
authors.forename: Heather C
authors.initials: HC
authors.lastname: Whalley
authors.forename: Pippa A
authors.initials: PA
authors.lastname: Thomson
authors.forename: William
authors.initials: W
authors.lastname: Hennah
authors.forename: Thomas W J
authors.initials: TW
authors.lastname: Moorhead
authors.forename: Killian A
authors.initials: KA
authors.lastname: Welch
authors.forename: Stephen
authors.initials: S
authors.lastname: Giles
authors.forename: Jeremy
authors.initials: J
authors.lastname: Hall
authors.forename: Eve C
authors.initials: EC
authors.lastname: Johnstone
authors.forename: Stephen M
authors.initials: SM
authors.lastname: Lawrie
authors.forename: David J
authors.initials: DJ
authors.lastname: Porteous
authors.forename: Verity J
authors.initials: VJ
authors.lastname: Brown
authors.forename: Andrew M
authors.initials: AM
authors.lastname: McIntosh
mesh_terms: D000328:Adult; D000704:Analysis of Variance; D001714:Bipolar Disorder / Q000235:genetics* / Q000473:pathology*; D001921:Brain / Q000098:blood supply / Q000473:pathology*; D001931:Brain Mapping; D005260:Female; D007839:Functional Laterality; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007091:Image Processing, Computer-Assisted; D008279:Magnetic Resonance Imaging; D008297:Male; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D009483:Neuropsychological Tests; D010100:Oxygen / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D011569:Psychiatric Status Rating Scales; D012307:Risk Factors; D012559:Schizophrenia / Q000235:genetics* / Q000473:pathology*
chemical_list: C412476:DISC1 protein, human; D009419:Nerve Tissue Proteins; D010100:Oxygen